# Clinical conceptualisation of PTSD in psilocybin treatment: disrupting a pre-determined and over-determined maladaptive interpretive framework

**Authors:** Nadav Liam Modlin, Victoria Williamson, Carolina Maggio, Joanne Stubley, Namik Kirlic, Anthony Cleare, James Rucker

PMC · DOI: 10.1177/20451253251342319 · Therapeutic Advances in Psychopharmacology · 2025-06-08

## TL;DR

This paper reviews how psilocybin, a psychedelic drug, may help treat PTSD by disrupting rigid, harmful thought patterns that maintain the disorder.

## Contribution

It introduces a novel conceptual framework for psilocybin treatment in PTSD, emphasizing disruption of maladaptive interpretive frameworks.

## Key findings

- Psilocybin shows potential in treating PTSD and related trauma disorders by altering entrenched cognitive patterns.
- The paper highlights the safety and efficacy of psilocybin in various trauma-related psychiatric conditions.
- Recommendations are provided for administering psilocybin safely in trauma-informed clinical settings.

## Abstract

Post-traumatic stress disorder (PTSD) and associated trauma and stressor-related disorders are common and debilitating, presenting significant treatment challenges due to their complex interplay of biological, cognitive, affective, somatic and social factors. Current treatments, while advancing and effective, yield limited efficacy for many individuals, underscoring the need for novel therapeutic approaches. This review explores the multifaceted nature of PTSD, emphasising its intricate predisposing and maintaining factors and explores the potential of psilocybin, a classical psychedelic, as a therapeutic agent. This review synthesises recent literature on the safety, efficacy and proposed mechanisms of action and change of psychedelic therapies for psychiatric conditions associated with traumatic stress, including treatment-resistant depression, end-of-life anxiety and anorexia nervosa. Correspondingly, it proposes a conceptual framework for psilocybin treatment in PTSD, framing the condition as a complex, maladaptive interpretive framework that is both predetermined and over-determined. A clinical narrative illustrates how psilocybin’s unique psychopharmacological properties and catalysed subjective effects may facilitate therapeutic progress by disrupting this rigid and restricting framework. Finally, we offer recommendations for the safe administration of psilocybin for traumatised patients in medical research settings, emphasising the importance of rigorous and trauma-informed protocols and comprehensive patient care.

## Linked entities

- **Chemicals:** psilocybin (PubChem CID 10624)
- **Diseases:** post-traumatic stress disorder (MONDO:0005146), anorexia nervosa (MONDO:0005351)

## Full-text entities

- **Diseases:** anxiety (MESH:D001007), trauma (MESH:D014947), anorexia nervosa (MESH:D000856), depression (MESH:D003866), psychiatric conditions (MESH:D001523), PTSD (MESH:D013313)
- **Chemicals:** psilocybin (MESH:D011562)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

177 references — full list in the complete paper: https://tomesphere.com/paper/PMC12146596/full.md

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Source: https://tomesphere.com/paper/PMC12146596